Abstract

Microfabrication Technologies For Engineering a Joint on Chip

Marcel Karperien, Professor, Developmental BioEngineering, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente

Osteoarthritis (OA) is a degenerative joint disease affecting more than 130.000.000 patients world-wide. The etiology of the disease is still poorly understood. While initially considered as a disease of cartilage it is now clear that the disease involves all tissues in the joint. A disease trigger in each of these tissues can initiate the onset of disease and each of these triggers converge over time in a similar disease presentation. Despite tremendous efforts in the recent past, the disease can still not be treated.  It is believed that lack of translational power of currently used in vitro and in vivo animal models can at least in part this lack of success. It has also become clear that currently used animal models poorly reflect the complexity of human disease nor do they allow the detailed study of the complex interactions between the different joint tissues at various stages of disease. To address these shortcomings my group has started the development of a joint-on-chip. The joint-on-chip has a modular chip design (Piluso et al., 2019). We are engineering chips for each individual tissue, i.e. cartilage, subchondral bone, synovium, ligament and/or meniscus which together form the joint. The individual chips are connected to each other through blood vessel mimicking microfluidic channels  as well as with a chip mimicking the intra-articular space. This latter chip will contain features allowing non-invasive imaging / sensing of inter tissue communication. Since movement is a critical and an essential feature in every joint, the individual chips can all be independently actuated mimicking both compression and shear stress. Prototype chips of the synovium and the cartilage including actuation have become available (Paggi et al., 2020). Additionally we developed various strategies for introducing cell laden membranes composed of natural polymers and/or tissue constructs in the chip. Finally, we have developed sensors that can assess local matrix metalloproteinase activity, a key factor driving joint degeneration on chip. In my presentation I will discuss various engineering aspects of our microfabrication technology platforms needed for recreating a representative and functional human joint. It is expected that these efforts will help us studying the pathophysiology of osteoarthritis and will accelerate the development of dearly needed osteoarthritis disease modifying treatments.